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Zeit-Not / Not-Zeit
(2017)
Theoretischer Hintergrund: Einflüsse von therapeutenorientiertem Kompetenz-Feedback in der Psychotherapieausbildung wurden bislang wenig untersucht.
Fragestellung: Wie gehen Ausbildungstherapeuten mit Feedback um? Welchen Einfluss hat ein regelmäßiges Kompetenz-Feedback auf die Qualität psychotherapeutischer Behandlungen (insbesondere Therapiesitzungen, therapeutische Beziehung, Person des Therapeuten, Supervision)?
Methode: Elf Therapeuten wurden mithilfe eines halbstrukturierten Interviewleitfadens befragt. Die Auswertung erfolgte mittels qualitativer Inhaltsanalyse nach Mayring (2015).
Ergebnisse: Das auf Basis der Interviews erstellte Kategoriensystem umfasste die Kategorien „Erwartungen an das Feedback“, „Wahrnehmung des Feedbacks“, „Verarbeitung von und Umgang mit Feedback“, „Folgen, Auswirkungen und Veränderungen durch Feedback“ sowie „Verbesserungswünsche“.
Schlussfolgerungen: Therapeuten streben eine Umsetzung des Feedbacks an, welches sich auf die Behandlung, die Supervision, die eigene Person und die therapeutische Beziehung auswirkt.
Kurz vor ihrem sechzigsten Geburtstag ist die europäische Union mit inneren und äußeren Herausforderungen konfrontiert und befindet sich in einer tiefen Krise. Am 1. März 2017 legte Kommissionspräsident Juncker das „Weißbuch über die Zukunft der Europäischen Union“ vor, in dem er verschiedene Szenarien darlegt und zur Diskussion über die anste-henden Entscheidungen einlädt. Diese Papier versteht sich als ein solcher Diskussionsbei-trag.
Im kognitiven Vulnerabilitäts-Stress-Modell der Depression von A.T. Beck (1967, 1976) spielen dysfunktionale Einstellungen bei der Entstehung von Depression in Folge von erlebtem Stress eine zentrale Rolle. Diese Theorie prägt seit Jahrzehnten die ätiologische Erforschung der Depression, jedoch ist die Bedeutung dysfunktionaler Einstellungen im Prozess der Entstehung einer Depression insbesondere im Kindes- und Jugendalter nach wie vor unklar. Die vorliegende Arbeit widmet sich einigen in der bisherigen Forschung wenig behandelten Fragen. Diese betreffen u. a. die Möglichkeit nichtlinearer Effekte dysfunktionaler Einstellungen, Auswirkungen einer Stichprobenselektion, Entwicklungseffekte sowie die Spezifität etwaiger Zusammenhänge für eine depressive Symptomatik.
Zur Beantwortung dieser Fragen wurden Daten von zwei Messzeitpunkten der PIER-Studie, eines großangelegten Längsschnittprojekts über Entwicklungsrisiken im Kindes- und Jugendalter, genutzt. Kinder und Jugendliche im Alter von 9 bis 18 Jahren berichteten zweimal im Abstand von ca. 20 Monaten im Selbstberichtsverfahren über ihre dysfunktionalen Einstellungen, Symptome aus verschiedenen Störungsbereichen sowie über eingetretene Lebensereignisse.
Die Ergebnisse liefern Evidenz für ein Schwellenmodell, in dem dysfunktionale Einstellungen unabhängig von Alter und Geschlecht nur im höheren Ausprägungsbereich eine Wirkung als Vulnerabilitätsfaktor zeigen, während im niedrigen Ausprägungsbereich keine Zusammenhänge zur späteren Depressivität bestehen. Eine Wirkung als Vulnerabilitätsfaktor war zudem nur in der Subgruppe der anfänglich weitgehend symptomfreien Kinder und Jugendlichen zu beobachten. Das Schwellenmodell erwies sich als spezifisch für eine depressive Symptomatik, es zeigten sich jedoch auch (teilweise ebenfalls nichtlineare) Effekte dysfunktionaler Einstellungen auf die Entwicklung von Essstörungssymptomen und aggressivem Verhalten. Bei 9- bis 13-jährigen Jungen standen dysfunktionale Einstellungen zudem in Zusammenhang mit einer Tendenz, Stress in Leistungskontexten herbeizuführen.
Zusammen mit den von Sahyazici-Knaak (2015) berichteten Ergebnissen aus der PIER-Studie weisen die Befunde darauf hin, dass dysfunktionale Einstellungen im Kindes- und Jugendalter – je nach betrachteter Subgruppe – Ursache, Symptom und Konsequenz der Depression darstellen können. Die in der vorliegenden Arbeit gezeigten nichtlinearen Effekte dysfunktionaler Einstellungen und die Effekte der Stichprobenselektion bieten eine zumindest teilweise Erklärung für die Heterogenität früherer Forschungsergebnisse. Insgesamt lassen sie auf komplexe – und nicht ausschließlich negative – Auswirkungen dysfunktionaler Einstellungen schließen. Für eine adäquate Beurteilung der „Dysfunktionalität“ der von A.T. Beck so betitelten Einstellungen erscheint daher eine Berücksichtigung der betrachteten Personengruppe, der absoluten Ausprägungen und der fraglichen Symptomgruppen geboten.
Die Arktis erwärmt sich schneller als der Rest der Erde. Die Auswirkungen manifestieren sich unter Anderem in einer verstärkten Erwärmung der arktischen Grenzschicht. Diese Arbeit befasst sich mit Wechselwirkungen zwischen synoptischen Zyklonen und der arktischen Atmosphäre auf lokalen bis überregionalen Skalen. Ausgangspunkt dafür sind Messdaten und Modellsimulationen für den Zeitraum der N-ICE2015 Expedition, die von Anfang Januar bis Ende Juni 2015 im arktischen Nordatlantiksektor stattgefunden hat.
Anhand von Radiosondenmessungen lassen sich Auswirkungen von synoptischen Zyklonen am deutlichsten im Winter erkennen, da sie durch die Advektion warmer und feuchter Luftmassen in die Arktis den Zustand der Atmosphäre von einem strahlungs-klaren in einen strahlungs-opaken ändern. Obwohl dieser scharfe Kontrast nur im Winter existiert, zeigt die Analyse, dass der integrierte Wasserdampf als Indikator für die Advektion von Luftmassen aus niedrigen Breiten in die Arktis auch im Frühjahr geeignet ist. Neben der Advektion von Luftmassen wird der Einfluss der Zyklonen auf die statische Stabilität charakterisiert. Beim Vergleich der N-ICE2015 Beobachtungen mit der SHEBA Kampagne (1997/1998), die über dickerem Eis stattfand, finden sich trotz der unterschiedlichen Meereisregime Ähnlichkeiten in der statischen Stabilität der Atmosphäre. Die beobachteten Differenzen in der Stabilität lassen sich auf Unterschiede in der synoptischen Aktivität zurückführen. Dies lässt vermuten, dass die dünnere Eisdecke auf saisonalen Zeitskalen nur einen geringen Einfluss auf die thermodynamische Struktur der arktischen Troposphäre besitzt, solange eine dicke Schneeschicht sie bedeckt. Ein weiterer Vergleich mit den parallel zur N-ICE2015 Kampagne gestarteten Radiosonden der AWIPEV Station in Ny-Åesund, Spitzbergen, macht deutlich, dass die synoptischen Zyklonen oberhalb der Orographie auf saisonalen Zeitskalen das Wettergeschehen bestimmen.
Des Weiteren werden für Februar 2015 die Auswirkungen von in der Vertikalen variiertem Nudging auf die Entwicklung der Zyklonen am Beispiel des hydrostatischen regionalen Klimamodells HIRHAM5 untersucht. Es zeigt sich, dass die Unterschiede zwischen den acht Modellsimulationen mit abnehmender Anzahl der genudgten Level zunehmen. Die größten Differenzen resultieren vornehmlich aus dem zeitlichen Versatz der Entwicklung synoptischer Zyklonen. Zur Korrektur des Zeitversatzes der Zykloneninitiierung genügt es bereits, Nudging in den unterstem 250 m der Troposphäre anzuwenden. Daneben findet sich zwischen den genudgten HIRHAM5-Simulation und den in situ Messungen der gleiche positive Temperaturbias, den auch ERA-Interim besitzt. Das freie HIRHAM hingegen reproduziert das positive Ende der N-ICE2015 Temperaturverteilung gut, besitzt aber einen starken negativen Bias, der sehr wahrscheinlich aus einer Unterschätzung des Feuchtegehalts resultiert. An Beispiel einer Zyklone wird gezeigt, dass Nudging Einfluss auf die Lage der Höhentiefs besitzt, die ihrerseits die Zyklonenentwicklung am Boden beeinflussen. Im Weiteren wird mittels eines für kleine Ensemblegrößen geeigneten Varianzmaßes eine statistische Einschätzung der Wirkung des Nudgings auf die Vertikale getroffen. Es wird festgestellt, dass die Ähnlichkeit der Modellsimulationen in der unteren Troposphäre generell höher ist als darüber und in 500 hPa ein lokales Minimum besitzt.
Im letzten Teil der Analyse wird die Wechselwirkung der oberen und unteren Stratosphäre anhand zuvor betrachteter Zyklonen mit Daten der ERA-Interim Reanalyse untersucht. Lage und Ausrichtung des Polarwirbels erzeugten ab Anfang Februar 2015 eine ungewöhnlich große Meridionalkomponente des Tropopausenjets, die Zugbahnen in die zentrale Arktis begünstigte. Am Beispiel einer Zyklone wird die Übereinstimmung der synoptischen Entwicklung mit den theoretischen Annahmen über den abwärts gerichteten Einfluss der Stratosphäre auf die Troposphäre hervorgehoben. Dabei spielt die nicht-lineare Wechselwirkung zwischen der Orographie Grönlands, einer Intrusion stratosphärischer Luft in die Troposphäre sowie einer in Richtung Arktis propagierender Rossby-Welle eine tragende Rolle. Als Indikator dieser Wechselwirkung werden horizontale Signaturen aus abwechselnd aufsteigender und absinkender Luft innerhalb der Troposphäre identifiziert.
The effect of cellulose-based polyelectrolytes on biomimetic calcium phosphate mineralization is described. Three cellulose derivatives, a polyanion, a polycation, and a polyzwitterion were used as additives. Scanning electron microscopy, X-ray diffraction, IR and Raman spectroscopy show that, depending on the composition of the starting solution, hydroxyapatite or brushite precipitates form. Infrared and Raman spectroscopy also show that significant amounts of nitrate ions are incorporated in the precipitates. Energy dispersive X-ray spectroscopy shows that the Ca/P ratio varies throughout the samples and resembles that of other bioinspired calcium phosphate hybrid materials. Elemental analysis shows that the carbon (i.e., polymer) contents reach 10% in some samples, clearly illustrating the formation of a true hybrid material. Overall, the data indicate that a higher polymer concentration in the reaction mixture favors the formation of polymer-enriched materials, while lower polymer concentrations or high precursor concentrations favor the formation of products that are closely related to the control samples precipitated in the absence of polymer. The results thus highlight the potential of (water-soluble) cellulose derivatives for the synthesis and design of bioinspired and bio-based hybrid materials.
The functioning of the surface water-groundwater interface as buffer, filter and reactive zone is important for water quality, ecological health and resilience of streams and riparian ecosystems. Solute and heat exchange across this interface is driven by the advection of water. Characterizing the flow conditions in the streambed is challenging as flow patterns are often complex and multidimensional, driven by surface hydraulic gradients and groundwater discharge. This thesis presents the results of an integrated approach of studies, ranging from the acquisition of field data, the development of analytical and numerical approaches to analyse vertical temperature profiles to the detailed, fully-integrated 3D numerical modelling of water and heat flux at the reach scale. All techniques were applied in order to characterize exchange flux between stream and groundwater, hyporheic flow paths and temperature patterns.
The study was conducted at a reach-scale section of the lowland Selke River, characterized by distinctive pool riffle sequences and fluvial islands and gravel bars. Continuous time series of hydraulic heads and temperatures were measured at different depths in the river bank, the hyporheic zone and within the river. The analyses of the measured diurnal temperature variation in riverbed sediments provided detailed information about the exchange flux between river and groundwater. Beyond the one-dimensional vertical water flow in the riverbed sediment, hyporheic and parafluvial flow patterns were identified. Subsurface flow direction and magnitude around fluvial islands and gravel bars at the study site strongly depended on the position around the geomorphological structures and on the river stage. Horizontal water flux in the streambed substantially impacted temperature patterns in the streambed. At locations with substantial horizontal fluxes the penetration depths of daily temperature fluctuations was reduced in comparison to purely vertical exchange conditions.
The calibrated and validated 3D fully-integrated model of reach-scale water and heat fluxes across the river-groundwater interface was able to accurately represent the real system. The magnitude and variations of the simulated temperatures matched the observed ones, with an average mean absolute error of 0.7 °C and an average Nash Sutcliffe Efficiency of 0.87. The simulation results showed that the water and heat exchange at the surface water-groundwater interface is highly variable in space and time with zones of daily temperature oscillations penetrating deep into the sediment and spots of daily constant temperature following the average groundwater temperature. The average hyporheic flow path temperature was found to strongly correlate with the flow path residence time (flow path length) and the temperature gradient between river and groundwater. Despite the complexity of these processes, the simulation results allowed the derivation of a general empirical relationship between the hyporheic residence times and temperature patterns. The presented results improve our understanding of the complex spatial and temporal dynamics of water flux and thermal processes within the shallow streambed. Understanding these links provides a general basis from which to assess hyporheic temperature conditions in river reaches.
Wahrnehmung und Heterogenität von Fach- und Lehramtsstudierenden im Kontext von Lehrveranstaltungen
(2017)
VS30, slope, H800 and f0
(2017)
The aim of this paper is to investigate the ability of various site-condition proxies (SCPs) to reduce ground-motion aleatory variability and evaluate how SCPs capture nonlinearity site effects. The SCPs used here are time-averaged shear-wave velocity in the top 30 m (VS30), the topographical slope (slope), the fundamental resonance frequency (f0) and the depth beyond which Vs exceeds 800 m/s (H800). We considered first the performance of each SCP taken alone and then the combined performance of the 6 SCP pairs [VS30–f0], [VS30–H800], [f0–slope], [H800–slope], [VS30–slope] and [f0–H800]. This analysis is performed using a neural network approach including a random effect applied on a KiK-net subset for derivation of ground-motion prediction equations setting the relationship between various ground-motion parameters such as peak ground acceleration, peak ground velocity and pseudo-spectral acceleration PSA (T), and Mw, RJB, focal depth and SCPs. While the choice of SCP is found to have almost no impact on the median groundmotion prediction, it does impact the level of aleatory uncertainty. VS30 is found to perform the best of single proxies
at short periods (T < 0.6 s), while f0 and H800 perform better at longer periods; considering SCP pairs leads to significant improvements, with particular emphasis on [VS30–H800] and [f0–slope] pairs. The results also indicate significant nonlinearity on the site terms for soft sites and that the most relevant loading parameter for characterising nonlinear site response is the “stiff” spectral ordinate at the considered period.
Vom Handeln und Schmusen
(2017)
Background
The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT.
Results
As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months.
Conclusion
LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors.
Vermessung im Sonnensystem
(2017)
Die bisherigen Missionen ins Sonnensystem lieferten eine enorme Fülle an Daten in unterschiedlichen Formaten und in Form von Bildern und digitalen Messergebnissen. Die Oberflächenprozesse der planetaren Körper, die mit Hilfe dieser Daten erforscht werden können, sind äußerst vielfältig und reichen von Einschlagskratern über Vulkanismus und Tektonik zu allen Formen der Erosion und Sedimentation. Um diese Prozesse verstehen zu können werden Verfahren angewendet, die für die Datenanalyse auf der Erde entwickelt wurden. Allerdings ist es notwendig all diese Verfahren zum Teil mit erheblichem Aufwand und unter Berücksichtigung der jeweiligen physikalischen Rahmenbedingungen anzupassen. Die Entwicklung kartographischer Verfahren zur Abstraktion der hier angesprochenen Informationen, also die Erfassung, geomorphologische Analyse und Visualisierung planetarer Oberflächen und Prozesse, hat jedoch gerade erst begonnen. Um diese Entwicklungen voranzutreiben, hat das Deutsche Zentrum für Luft- und Raumfahrt in Kooperation mit der Universität Potsdam (Institut für Geographie, Fachgruppe Geoinformatik, Prof. Dr. Asche), im Rahmen von Dissertationen und Forschungsvorhaben, in einem ersten Schritt kartographische Analyseverfahren für den Mars und die Asteroiden Ceres und Vesta entwickelt.
In this study, we validate and compare elevation accuracy and geomorphic metrics of satellite-derived digital elevation models (DEMs) on the southern Central Andean Plateau. The plateau has an average elevation of 3.7 km and is characterized by diverse topography and relief, lack of vegetation, and clear skies that create ideal conditions for remote sensing. At 30m resolution, SRTM-C, ASTER GDEM2, stacked ASTER L1A stereopair DEM, ALOS World 3D, and TanDEM-X have been analyzed. The higher-resolution datasets include 12m TanDEM-X, 10m single-CoSSC TerraSAR-X/TanDEM-X DEMs, and 5m ALOS World 3D. These DEMs are state of the art for optical (ASTER and ALOS) and radar (SRTM-C and TanDEM-X) spaceborne sensors. We assessed vertical accuracy by comparing standard deviations of the DEM elevation versus 307 509 differential GPS measurements across 4000m of elevation. For the 30m DEMs, the ASTER datasets had the highest vertical standard deviation at > 6.5 m, whereas the SRTM-C, ALOS World 3D, and TanDEM-X were all < 3.5 m. Higher-resolution DEMs generally had lower uncertainty, with both the 12m TanDEM-X and 5m ALOSWorld 3D having < 2m vertical standard deviation. Analysis of vertical uncertainty with respect to terrain elevation, slope, and aspect revealed the low uncertainty across these attributes for SRTM-C (30 m), TanDEM-X (12–30 m), and ALOS World 3D (5–30 m). Single-CoSSC TerraSAR-X/TanDEM-X 10m DEMs and the 30m ASTER GDEM2 displayed slight aspect biases, which were removed in their stacked counterparts (TanDEM-X and ASTER Stack). Based on low vertical standard deviations and visual inspection alongside optical satellite data, we selected the 30m SRTM-C, 12–30m TanDEM-X, 10m single-CoSSC TerraSAR-X/TanDEM-X, and 5m ALOS World 3D for geomorphic metric comparison in a 66 km2 catchment with a distinct river knickpoint. Consistent m=n values were found using chi plot channel profile analysis, regardless of DEM type and spatial resolution. Slope, curvature, and drainage area were calculated and plotting schemes were used to assess basin-wide differences in the hillslope-to-valley transition related to the knickpoint. While slope and hillslope length measurements vary little between datasets, curvature displays higher magnitude measurements with fining resolution. This is especially true for the optical 5m ALOS World 3D DEM, which demonstrated high-frequency noise in 2–8 pixel steps through a Fourier frequency analysis. The improvements in accurate space-radar DEMs (e.g., TanDEM-X) for geomorphometry are promising, but airborne or terrestrial data are still necessary for meter-scale analysis.
Background: Plasma concentration of retinol is an accepted indicator to assess the vitamin A (retinol) status in cattle. However, the determination of vitamin A requires a time consuming multi-step procedure, which needs specific equipment to perform extraction, centrifugation or saponification prior to high-performance liquid chromatography (HPLC).
Methods: The concentrations of retinol in whole blood (n = 10), plasma (n = 132) and serum (n = 61) were measured by a new rapid cow-side test (iCheck™ FLUORO) and compared with those by HPLC in two independent laboratories in Germany (DE) and Japan (JP).
Results: Retinol concentrations in plasma ranged from 0.033 to 0.532 mg/L, and in serum from 0.043 to 0.360 mg/L (HPLC method). No significant differences in retinol levels were observed between the new rapid cow-side test and HPLC performed in different laboratories (HPLC vs. iCheck™ FLUORO: 0.320 ± 0.047 mg/L vs. 0.333 ± 0.044 mg/L, and 0.240 ± 0.096 mg/L vs. 0.241 ± 0.069 mg/L, lab DE and lab JP, respectively). A similar comparability was observed when whole blood was used (HPLC vs. iCheck™ FLUORO: 0.353 ± 0.084 mg/L vs. 0.341 ± 0.064 mg/L). Results showed a good agreement between both methods based on correlation coefficients of r2 = 0.87 (P < 0.001) and Bland-Altman blots revealed no significant bias for all comparison.
Conclusions: With the new rapid cow-side test (iCheck™ FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle.
Statistics Canada, Canada’s national statistics agency, offers a suite of spatial
files for mapping and analysis of its various population data products. The following
article showcases possibilities and shortfalls of the existing spatial files
for mapping population data, and provides an overview of the structure of the
available boundary files from the regional to the dissemination block level. Due
to Canada’s highly dispersed population, mapping its distribution and density can
be challenging. Common mapping techniques such as the choropleth method are
suitable only for mapping spatially high resolution data such as data at the dissemination
area level. To allow for mapping of population data at less detailed levels
such as census divisions or provinces, Statistics Canada has created a so-called
ecumene boundary file which outlines the inhabited area of Canada and can be
used to more accurately visualize Canada’s population distribution and density.
Using behavioral observation for the longitudinal study of anger regulation in middle childhood
(2017)
Assessing anger regulation via self-reports is fraught with problems, especially among children. Behavioral observation provides an ecologically valid alternative for measuring anger regulation. The present study uses data from two waves of a longitudinal study to present a behavioral observation approach for measuring anger regulation in middle childhood. At T1, 599 children from Germany (6–10 years old) were observed during an anger eliciting task, and the use of anger regulation strategies was coded. At T2, 3 years later, the observation was repeated with an age-appropriate version of the same task. Partial metric measurement invariance over time demonstrated the structural equivalence of the two versions. Maladaptive anger regulation between the two time points showed moderate stability. Validity was established by showing correlations with aggressive behavior, peer problems, and conduct problems (concurrent and predictive criterion validity). The study presents an ecologically valid and economic approach to assessing anger regulation strategies in situations.
Background: Although the benefits for health of physical activity (PA) are well documented, the majority of the population is unable to implement present recommendations into daily routine. Mobile health (mHealth) apps could help increase the level of PA. However, this is contingent on the interest of potential users.
Objective: The aim of this study was the explorative, nuanced determination of the interest in mHealth apps with respect to PA among students and staff of a university.
Methods: We conducted a Web-based survey from June to July 2015 in which students and employees from the University of Potsdam were asked about their activity level, interest in mHealth fitness apps, chronic diseases, and sociodemographic parameters.
Results: A total of 1217 students (67.30%, 819/1217; female; 26.0 years [SD 4.9]) and 485 employees (67.5%, 327/485; female; 42.7 years [SD 11.7]) participated in the survey. The recommendation for PA (3 times per week) was not met by 70.1% (340/485) of employees and 52.67% (641/1217) of students. Within these groups, 53.2% (341/641 students) and 44.2% (150/340 employees)—independent of age, sex, body mass index (BMI), and level of education or professional qualification—indicated an interest in mHealth fitness apps.
Conclusions: Even in a younger, highly educated population, the majority of respondents reported an insufficient level of PA. About half of them indicated their interest in training support. This suggests that the use of personalized mobile fitness apps may become increasingly significant for a positive change of lifestyle.
Die Femtosekundendynamik nach resonanten Photoanregungen mit optischen und Röntgenpulsen ermöglicht eine selektive Verformung von chemischen N‐H‐ und N‐C‐Bindungen in 2‐Thiopyridon in wässriger Lösung. Die Untersuchung der orbitalspezifischen elektronischen Struktur und ihrer Dynamik auf ultrakurzen Zeitskalen mit resonanter inelastischer Röntgenstreuung an der N1s‐Resonanz am Synchrotron und dem Freie‐Elektronen‐Laser LCLS in Kombination mit quantenchemischen Multikonfigurationsberechnungen erbringen den direkten Nachweis dieser kontrollierten photoinduzierten Molekülverformungen und ihrer ultrakurzen Zeitskala.
Background: Inferring regulatory interactions between genes from transcriptomics time-resolved data, yielding reverse engineered gene regulatory networks, is of paramount importance to systems biology and bioinformatics studies. Accurate methods to address this problem can ultimately provide a deeper insight into the complexity, behavior, and functions of the underlying biological systems. However, the large number of interacting genes coupled with short and often noisy time-resolved read-outs of the system renders the reverse engineering a challenging task. Therefore, the development and assessment of methods which are computationally efficient, robust against noise, applicable to short time series data, and preferably capable of reconstructing the directionality of the regulatory interactions remains a pressing research problem with valuable applications.
Results: Here we perform the largest systematic analysis of a set of similarity measures and scoring schemes within the scope of the relevance network approach which are commonly used for gene regulatory network reconstruction from time series data. In addition, we define and analyze several novel measures and schemes which are particularly suitable for short transcriptomics time series. We also compare the considered 21 measures and 6 scoring schemes according to their ability to correctly reconstruct such networks from short time series data by calculating summary statistics based on the corresponding specificity and sensitivity. Our results demonstrate that rank and symbol based measures have the highest performance in inferring regulatory interactions. In addition, the proposed scoring scheme by asymmetric weighting has shown to be valuable in reducing the number of false positive interactions. On the other hand, Granger causality as well as information-theoretic measures, frequently used in inference of regulatory networks, show low performance on the short time series analyzed in this study.
Conclusions: Our study is intended to serve as a guide for choosing a particular combination of similarity measures and scoring schemes suitable for reconstruction of gene regulatory networks from short time series data. We show that further improvement of algorithms for reverse engineering can be obtained if one considers measures that are rooted in the study of symbolic dynamics or ranks, in contrast to the application of common similarity measures which do not consider the temporal character of the employed data. Moreover, we establish that the asymmetric weighting scoring scheme together with symbol based measures (for low noise level) and rank based measures (for high noise level) are the most suitable choices.
The femtosecond excited-state dynamics following resonant photoexcitation enable the selective deformation of N-H and N-C chemical bonds in 2-thiopyridone in aqueous solution with optical or X-ray pulses. In combination with multiconfigurational quantum-chemical calculations, the orbital-specific electronic structure and its ultrafast dynamics accessed with resonant inelastic X-ray scattering at the N 1s level using synchrotron radiation and the soft X-ray free-electron laser LCLS provide direct evidence for this controlled photoinduced molecular deformation and its ultrashort time-scale.
Many studies demonstrated interactions between number processing and either spatial codes (effects of spatial-numerical associations) or visual size-related codes (size-congruity effect). However, the interrelatedness of these two number couplings is still unclear. The present study examines the simultaneous occurrence of space- and size-numerical congruency effects and their interactions both within and across trials, in a magnitude judgment task physically small or large digits were presented left or right from screen center. The reaction times analysis revealed that space- and size-congruency effects coexisted in parallel and combined additively. Moreover, a selective sequential modulation of the two congruency effects was found. The size-congruency effect was reduced after size incongruent trials. The space-congruency effect, however, was only affected by the previous space congruency. The observed independence of spatial-numerical and within magnitude associations is interpreted as evidence that the two couplings reflect Different attributes of numerical meaning possibly related to orginality and cardinality.
In the context of back pain, great emphasis has been placed on the importance of trunk stability, especially in situations requiring compensation of repetitive, intense loading induced during high-performance activities, e.g., jumping or landing. This study aims to evaluate trunk muscle activity during drop jump in adolescent athletes with back pain (BP) compared to athletes without back pain (NBP). Eleven adolescent athletes suffering back pain (BP: m/f: n = 4/7; 15.9 ± 1.3 y; 176 ± 11 cm; 68 ± 11 kg; 12.4 ± 10.5 h/we training) and 11 matched athletes without back pain (NBP: m/f: n = 4/7; 15.5 ± 1.3 y; 174 ± 7 cm; 67 ± 8 kg; 14.9 ± 9.5 h/we training) were evaluated. Subjects conducted 3 drop jumps onto a force plate (ground reaction force). Bilateral 12-lead SEMG (surface Electromyography) was applied to assess trunk muscle activity. Ground contact time [ms], maximum vertical jump force [N], jump time [ms] and the jump performance index [m/s] were calculated for drop jumps. SEMG amplitudes (RMS: root mean square [%]) for all 12 single muscles were normalized to MIVC (maximum isometric voluntary contraction) and analyzed in 4 time windows (100 ms pre- and 200 ms post-initial ground contact, 100 ms pre- and 200 ms post-landing) as outcome variables. In addition, muscles were grouped and analyzed in ventral and dorsal muscles, as well as straight and transverse trunk muscles. Drop jump ground reaction force variables did not differ between NBP and BP (p > 0.05). Mm obliquus externus and internus abdominis presented higher SEMG amplitudes (1.3–1.9-fold) for BP (p < 0.05). Mm rectus abdominis, erector spinae thoracic/lumbar and latissimus dorsi did not differ (p > 0.05). The muscle group analysis over the whole jumping cycle showed statistically significantly higher SEMG amplitudes for BP in the ventral (p = 0.031) and transverse muscles (p = 0.020) compared to NBP. Higher activity of transverse, but not straight, trunk muscles might indicate a specific compensation strategy to support trunk stability in athletes with back pain during drop jumps. Therefore, exercises favoring the transverse trunk muscles could be recommended for back pain treatment.
Trunk loading and back pain
(2017)
An essential function of the trunk is the compensation of external forces and loads in order to guarantee stability. Stabilising the trunk during sudden, repetitive loading in everyday tasks, as well as during performance is important in order to protect against injury. Hence, reduced trunk stability is accepted as a risk factor for the development of back pain (BP). An altered activity pattern including extended response and activation times as well as increased co-contraction of the trunk muscles as well as a reduced range of motion and increased movement variability of the trunk are evident in back pain patients (BPP). These differences to healthy controls (H) have been evaluated primarily in quasi-static test situations involving isolated loading directly to the trunk. Nevertheless, transferability to everyday, dynamic situations is under debate. Therefore, the aim of this project is to analyse 3-dimensional motion and neuromuscular reflex activity of the trunk as response to dynamic trunk loading in healthy (H) and back pain patients (BPP).
A measurement tool was developed to assess trunk stability, consisting of dynamic test situations. During these tests, loading of the trunk is generated by the upper and lower limbs with and without additional perturbation. Therefore, lifting of objects and stumbling while walking are adequate represents. With the help of a 12-lead EMG, neuromuscular activity of the muscles encompassing the trunk was assessed. In addition, three-dimensional trunk motion was analysed using a newly developed multi-segmental trunk model. The set-up was checked for reproducibility as well as validity. Afterwards, the defined measurement set-up was applied to assess trunk stability in comparisons of healthy and back pain patients.
Clinically acceptable to excellent reliability could be shown for the methods (EMG/kinematics) used in the test situations. No changes in trunk motion pattern could be observed in healthy adults during continuous loading (lifting of objects) of different weights. In contrast, sudden loading of the trunk through perturbations to the lower limbs during walking led to an increased neuromuscular activity and ROM of the trunk. Moreover, BPP showed a delayed muscle response time and extended duration until maximum neuromuscular activity in response to sudden walking perturbations compared to healthy controls. In addition, a reduced lateral flexion of the trunk during perturbation could be shown in BPP.
It is concluded that perturbed gait seems suitable to provoke higher demands on trunk stability in adults. The altered neuromuscular and kinematic compensation pattern in back pain patients (BPP) can be interpreted as increased spine loading and reduced trunk stability in patients. Therefore, this novel assessment of trunk stability is suitable to identify deficits in BPP. Assignment of affected BPP to therapy interventions with focus on stabilisation of the trunk aiming to improve neuromuscular control in dynamic situations is implied. Hence, sensorimotor training (SMT) to enhance trunk stability and compensation of unexpected sudden loading should be preferred.
Trends in precipitation over Germany and the Rhine basin related to changes in weather patterns
(2017)
Precipitation as the central meteorological feature for agriculture, water security, and human well-being amongst others, has gained special attention ever since. Lack of precipitation may have devastating effects such as crop failure and water scarcity. Abundance of precipitation, on the other hand, may as well result in hazardous events such as flooding and again crop failure. Thus, great effort has been spent on tracking changes in precipitation and relating them to underlying processes. Particularly in the face of global warming and given the link between temperature and atmospheric water holding capacity, research is needed to understand the effect of climate change on precipitation.
The present work aims at understanding past changes in precipitation and other meteorological variables. Trends were detected for various time periods and related to associated changes in large-scale atmospheric circulation. The results derived in this thesis may be used as the foundation for attributing changes in floods to climate change. Assumptions needed for the downscaling of large-scale circulation model output to local climate stations are tested and verified here.
In a first step, changes in precipitation over Germany were detected, focussing not only on precipitation totals, but also on properties of the statistical distribution, transition probabilities as a measure for wet/dry spells, and extreme precipitation events.
Shifting the spatial focus to the Rhine catchment as one of the major water lifelines of Europe and the largest river basin in Germany, detected trends in precipitation and other meteorological variables were analysed in relation to states of an ``optimal'' weather pattern classification. The weather pattern classification was developed seeking the best skill in explaining the variance of local climate variables.
The last question addressed whether observed changes in local climate variables are attributable to changes in the frequency of weather patterns or rather to changes within the patterns itself. A common assumption for a downscaling approach using weather patterns and a stochastic weather generator is that climate change is expressed only as a changed occurrence of patterns with the pattern properties remaining constant. This assumption was validated and the ability of the latest generation of general circulation models to reproduce the weather patterns was evaluated.
% Paper 1
Precipitation changes in Germany in the period 1951-2006 can be summarised briefly as negative in summer and positive in all other seasons. Different precipitation characteristics confirm the trends in total precipitation: while winter mean and extreme precipitation have increased, wet spells tend to be longer as well (expressed as increased probability for a wet day followed by another wet day). For summer the opposite was observed: reduced total precipitation, supported by decreasing mean and extreme precipitation and reflected in an increasing length of dry spells.
Apart from this general summary for the whole of Germany, the spatial distribution within the country is much more differentiated. Increases in winter precipitation are most pronounced in the north-west and south-east of Germany, while precipitation increases are highest in the west for spring and in the south for autumn. Decreasing summer precipitation was observed in most regions of Germany, with particular focus on the south and west.
The seasonal picture, however, was again differently represented in the contributing months, e.g.\ increasing autumn precipitation in the south of Germany is formed by strong trends in the south-west in October and in the south-east in November. These results emphasise the high spatial and temporal organisation of precipitation changes.
% Paper 2
The next step towards attributing precipitation trends to changes in large-scale atmospheric patterns was the derivation of a weather pattern classification that sufficiently stratifies the local climate variables under investigation. Focussing on temperature, radiation, and humidity in addition to precipitation, a classification based on mean sea level pressure, near-surface temperature, and specific humidity was found to have the best skill in explaining the variance of the local variables. A rather high number of 40 patterns was selected, allowing typical pressure patterns being assigned to specific seasons by the associated temperature patterns. While the skill in explaining precipitation variance is rather low, better skill was achieved for radiation and, of course, temperature.
Most of the recent GCMs from the CMIP5 ensemble were found to reproduce these weather patterns sufficiently well in terms of frequency, seasonality, and persistence.
% Paper 3
Finally, the weather patterns were analysed for trends in pattern frequency, seasonality, persistence, and trends in pattern-specific precipitation and temperature. To overcome uncertainties in trend detection resulting from the selected time period, all possible periods in 1901-2010 with a minimum length of 31 years were considered. Thus, the assumption of a constant link between patterns and local weather was tested rigorously. This assumption was found to hold true only partly. While changes in temperature are mainly attributable to changes in pattern frequency, for precipitation a substantial amount of change was detected within individual patterns.
Magnitude and even sign of trends depend highly on the selected time period. The frequency of certain patterns is related to the long-term variability of large-scale circulation modes.
Changes in precipitation were found to be heterogeneous not only in space, but also in time - statements on trends are only valid for the specific time period under investigation. While some part of the trends can be attributed to changes in the large-scale circulation, distinct changes were found within single weather patterns as well.
The results emphasise the need to analyse multiple periods for thorough trend detection wherever possible and add some note of caution to the application of downscaling approaches based on weather patterns, as they might misinterpret the effect of climate change due to neglecting within-type trends.
Translating innovation
(2017)
This doctoral thesis studies the process of innovation adoption in public administrations, addressing the research question of how an innovation is translated to a local context. The study empirically explores Design Thinking as a new problem-solving approach introduced by a federal government organisation in Singapore. With a focus on user-centeredness, collaboration and iteration Design Thinking seems to offer a new way to engage recipients and other stakeholders of public services as well as to re-think the policy design process from a user’s point of view. Pioneered in the private sector, early adopters of the methodology include civil services in Australia, Denmark, the United Kingdom, the United States as well as Singapore. Hitherto, there is not much evidence on how and for which purposes Design Thinking is used in the public sector.
For the purpose of this study, innovation adoption is framed in an institutionalist perspective addressing how concepts are translated to local contexts. The study rejects simplistic views of the innovation adoption process, in which an idea diffuses to another setting without adaptation. The translation perspective is fruitful because it captures the multidimensionality and ‘messiness’ of innovation adoption. More specifically, the overall research question addressed in this study is: How has Design Thinking been translated to the local context of the public sector organisation under investigation? And from a theoretical point of view: What can we learn from translation theory about innovation adoption processes?
Moreover, there are only few empirical studies of organisations adopting Design Thinking and most of them focus on private organisations. We know very little about how Design Thinking is embedded in public sector organisations. This study therefore provides further empirical evidence of how Design Thinking is used in a public sector organisation, especially with regards to its application to policy work which has so far been under-researched.
An exploratory single case study approach was chosen to provide an in-depth analysis of the innovation adoption process. Based on a purposive, theory-driven sampling approach, a Singaporean Ministry was selected because it represented an organisational setting in which Design Thinking had been embedded for several years, making it a relevant case with regard to the research question. Following a qualitative research design, 28 semi-structured interviews (45-100 minutes) with employees and managers were conducted. The interview data was triangulated with observations and documents, collected during a field research research stay in Singapore.
The empirical study of innovation adoption in a single organisation focused on the intra-organisational perspective, with the aim to capture the variations of translation that occur during the adoption process. In so doing, this study opened the black box often assumed in implementation studies. Second, this research advances translation studies not only by showing variance, but also by deriving explanatory factors. The main differences in the translation of Design Thinking occurred between service delivery and policy divisions, as well as between the first adopter and the rest of the organisation. For the intra-organisational translation of Design Thinking in the Singaporean Ministry the following five factors played a role: task type, mode of adoption, type of expertise, sequence of adoption, and the adoption of similar practices.
Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60–72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality (p < 0.05) and the auditory modality (p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination.
With its transparent orthography, Standard Indonesian is spoken by over 160 million inhabitants and is the primary language of instruction in education and the government in Indonesia. An assessment battery of reading and reading-related skills was developed as a starting point for the diagnosis of dyslexia in beginner learners. Founded on the International Dyslexia Association’s definition of dyslexia, the test battery comprises nine empirically motivated reading and reading-related tasks assessing word reading, pseudoword reading, arithmetic, rapid automatized naming, phoneme deletion, forward and backward digit span, verbal fluency, orthographic choice (spelling), and writing. The test was validated by computing the relationships between the outcomes on the reading-skills and reading-related measures by means of correlation and factor analyses. External variables, i.e., school grades and teacher ratings of the reading and learning abilities of individual students, were also utilized to provide evidence of its construct validity. Four variables were found to be significantly related with reading-skill measures: phonological awareness, rapid naming, spelling, and digit span. The current study on reading development in Standard Indonesian confirms findings from other languages with transparent orthographies and suggests a test battery including preliminary norm scores for screening and assessment of elementary school children learning to read Standard Indonesian.
As an emerging sub-field of music information retrieval (MIR), music imagery information retrieval (MIIR) aims to retrieve information from brain activity recorded during music cognition–such as listening to or imagining music pieces. This is a highly inter-disciplinary endeavor that requires expertise in MIR as well as cognitive neuroscience and psychology. The OpenMIIR initiative strives to foster collaborations between these fields to advance the state of the art in MIIR. As a first step, electroencephalography (EEG) recordings of music perception and imagination have been made publicly available, enabling MIR researchers to easily test and adapt their existing approaches for music analysis like fingerprinting, beat tracking or tempo estimation on this new kind of data. This paper reports on first results of MIIR experiments using these OpenMIIR datasets and points out how these findings could drive new research in cognitive neuroscience.
We present a setup combining a liquid flatjet sample delivery and a MHz laser system for time-resolved soft X-ray absorption measurements of liquid samples at the high brilliance undulator beamline UE52-SGM at Bessy II yielding unprecedented statistics in this spectral range. We demonstrate that the efficient detection of transient absorption changes in transmission mode enables the identification of photoexcited species in dilute samples. With iron(II)-trisbipyridine in aqueous solution as a benchmark system, we present absorption measurements at various edges in the soft X-ray regime. In combination with the wavelength tunability of the laser system, the set-up opens up opportunities to study the photochemistry of many systems at low concentrations, relevant to materials sciences, chemistry, and biology.
We introduce three strategies for the analysis of financial time series based on time averaged observables. These comprise the time averaged mean squared displacement (MSD) as well as the ageing and delay time methods for varying fractions of the financial time series. We explore these concepts via statistical analysis of historic time series for several Dow Jones Industrial indices for the period from the 1960s to 2015. Remarkably, we discover a simple universal law for the delay time averaged MSD. The observed features of the financial time series dynamics agree well with our analytical results for the time averaged measurables for geometric Brownian motion, underlying the famed Black–Scholes–Merton model. The concepts we promote here are shown to be useful for financial data analysis and enable one to unveil new universal features of stock market dynamics.
In October 2016, following a campaign led by Labour Peer Lord
Alfred Dubs, the first child asylum-seekers allowed entry to the UK
under new legislation (the ‘Dubs amendment’) arrived in England.
Their arrival was captured by a heavy media presence, and very
quickly doubts were raised by right-wing tabloids and politicians
about their age. In this article, I explore the arguments
underpinning the Dubs campaign and the media coverage of
the children’s arrival as a starting point for interrogating
representational practices around children who seek asylum. I
illustrate how the campaign was premised on a universal politics
of childhood that inadvertently laid down the terms on which
these children would be given protection, namely their innocence.
The universality of childhood fuels public sympathy for child
asylum-seekers, underlies the ‘child first, migrant second’
approach advocated by humanitarian organisations, and it was a
key argument in the ‘Dubs amendment’. Yet the campaign
highlights how representations of child asylum-seekers rely on
codes that operate to identify ‘unchildlike’ children. As I show, in
the context of the criminalisation of undocumented migrants‘,
childhood is no longer a stable category which guarantees
protection, but is subject to scrutiny and suspicion and can,
ultimately, be disproved.
Thermal cis-trans isomerization of azobenzene studied by path sampling and QM/MM stochastic dynamics
(2017)
Azobenzene-based molecular photoswitches have extensively been applied to biological systems, involving photo-control of peptides, lipids and nucleic acids. The isomerization between the stable trans and the metastable cis state of the azo moieties leads to pronounced changes in shape and other physico-chemical properties of the molecules into which they are incorporated. Fast switching can be induced via transitions to excited electronic states and fine-tuned by a large number of different substituents at the phenyl rings. But a rational design of tailor-made azo groups also requires control of their stability in the dark, the half-lifetime of the cis isomer. In computational chemistry, thermally activated barrier crossing on the ground state Born-Oppenheimer surface can efficiently be estimated with Eyring’s transition state theory (TST) approach; the growing complexity of the azo moiety and a rather heterogeneous environment, however, may render some of the underlying simplifying assumptions problematic.
In this dissertation, a computational approach is established to remove two restrictions at once: the environment is modeled explicitly by employing a quantum mechanical/molecular mechanics (QM/MM) description; and the isomerization process is tracked by analyzing complete dynamical pathways between stable states. The suitability of this description is validated by using two test systems, pure azo benzene and a derivative with electron donating and electron withdrawing substituents (“push-pull” azobenzene). Each system is studied in the gas phase, in toluene and in polar DMSO solvent. The azo molecules are treated at the QM level using a very recent, semi-empirical approximation to density functional theory (density functional tight binding approximation). Reactive pathways are sampled by implementing a version of the so-called transition path sampling method (TPS), without introducing any bias into the system dynamics. By analyzing ensembles of reactive trajectories, the change in isomerization pathway from linear inversion to rotation in going from apolar to polar solvent, predicted by the TST approach, could be verified for the push-pull derivative. At the same time, the mere presence of explicit solvation is seen to broaden the distribution of isomerization pathways, an effect TST cannot account for.
Using likelihood maximization based on the TPS shooting history, an improved reaction coordinate was identified as a sine-cosine combination of the central bend angles and the rotation dihedral, r (ω,α,α′). The computational van’t Hoff analysis for the activation entropies was performed to gain further insight into the differential role of solvent for the case of the unsubstituted and the push-pull azobenzene. In agreement with the experiment, it yielded positive activation entropies for azobenzene in the DMSO solvent while negative for the push-pull derivative, reflecting the induced ordering of solvent around the more dipolar transition state associated to the latter compound. Also, the dynamically corrected rate constants were evaluated using the reactive flux approach where an increase comparable to the experimental one was observed for a high polarity medium for both azobenzene derivatives.
Rezensiertes Werk
Theresa Biberauer u. George Walkden (Hgg.): Syntax over Time: Lexical, Morphological, and Information – Structural Interactions - Oxford, Oxford University Press, 2015, 418 S.
Einleitung: Die Erdnussallergie zählt zu den häufigsten Nahrungsmittelallergien im Kindesalter. Bereits kleine Mengen Erdnuss (EN) können zu schweren allergischen Reaktionen führen. EN ist der häufigste Auslöser einer lebensbedrohlichen Anaphylaxie bei Kindern und Jugendlichen. Im Gegensatz zu anderen frühkindlichen Nahrungsmittelallergien entwickeln Patienten mit einer EN-Allergie nur selten eine natürliche Toleranz. Seit mehreren Jahren wird daher an kausalen Therapiemöglichkeiten für EN-Allergiker, insbesondere an der oralen Immuntherapie (OIT), geforscht. Erste kleinere Studien zur OIT bei EN-Allergie zeigten erfolgsversprechende Ergebnisse. Im Rahmen einer randomisierten, doppelblind, Placebo-kontrollierten Studie mit größerer Fallzahl werden in der vorliegenden Arbeit die klinische Wirksamkeit und Sicherheit dieser Therapieoption bei Kindern mit EN-Allergie genauer evaluiert. Des Weiteren werden immunologische Veränderungen sowie die Lebensqualität und Therapiebelastung unter OIT untersucht.
Methoden: Kinder zwischen 3-18 Jahren mit einer IgE-vermittelten EN-Allergie wurden in die Studie eingeschlossen. Vor Beginn der OIT wurde eine orale Provokation mit EN durchgeführt. Die Patienten wurden 1:1 randomisiert und entsprechend der Verum- oder Placebogruppe zugeordnet. Begonnen wurde mit 2-120 mg EN bzw. Placebo pro Tag, abhängig von der Reaktionsdosis bei der oralen Provokation. Zunächst wurde die tägliche OIT-Dosis alle zwei Wochen über etwa 14 Monate langsam bis zu einer Erhaltungsdosis von mindestens 500 mg EN (= 125 mg EN-Protein, ~ 1 kleine EN) bzw. Placebo gesteigert. Die maximal erreichte Dosis wurde dann über zwei Monate täglich zu Hause verabreicht. Im Anschluss erfolgte erneut eine orale Provokation mit EN. Der primäre Endpunkt der Studie war die Anzahl an Patienten der Verum- und Placebogruppe, die unter oraler Provokation nach OIT ≥1200 mg EN vertrugen (=„partielle Desensibilisierung“). Sowohl vor als auch nach OIT wurde ein Hautpricktest mit EN durchgeführt und EN-spezifisches IgE und IgG4 im Serum bestimmt. Außerdem wurden die Basophilenaktivierung sowie die Ausschüttung von T-Zell-spezifischen Zytokinen nach Stimulation mit EN in vitro gemessen. Anhand von Fragebögen wurde die Lebensqualität vor und nach OIT sowie die Therapiebelastung während OIT erfasst.
Ergebnisse: 62 Patienten wurden in die Studie eingeschlossen und randomisiert. Nach etwa 16 Monaten unter OIT zeigten 74,2% (23/31) der Patienten der Verumgruppe und nur 16,1% (5/31) der Placebogruppe eine „partielle Desensibilisierung“ gegenüber EN (p<0,001). Im Median vertrugen Patienten der Verumgruppe 4000 mg EN (~8 kleine EN) unter der Provokation nach OIT wohingegen Patienten der Placebogruppe nur 80 mg EN (~1/6 kleine EN) vertrugen (p<0,001). Fast die Hälfte der Patienten der Verumgruppe (41,9%) tolerierten die Höchstdosis von 18 g EN unter Provokation („komplette Desensibilisierung“). Es zeigte sich ein vergleichbares Sicherheitsprofil unter Verum- und Placebo-OIT in Bezug auf objektive Nebenwirkungen. Unter Verum-OIT kam es jedoch signifikant häufiger zu subjektiven Nebenwirkungen wie oralem Juckreiz oder Bauchschmerzen im Vergleich zu Placebo (3,7% der Verum-OIT-Gaben vs. 0,5% der Placebo-OIT-Gaben, p<0,001). Drei Kinder der Verumgruppe (9,7%) und sieben Kinder der Placebogruppe (22,6%) beendeten die Studie vorzeitig, je zwei Patienten beider Gruppen aufgrund von Nebenwirkungen. Im Gegensatz zu Placebo, zeigten sich unter Verum-OIT signifikante immunologische Veränderungen. So kam es zu einer Abnahme des EN-spezifischen Quaddeldurchmessers im Hautpricktest, einem Anstieg der EN-spezifischen IgG4-Werte im Serum sowie zu einer verminderten EN-spezifischen Zytokinsekretion, insbesondere der Th2-spezifischen Zytokine IL-4 und IL-5. Hinsichtlich der EN-spezifischen IgE-Werte sowie der EN-spezifischen Basophilenaktivierung zeigten sich hingegen keine Veränderungen unter OIT. Die Lebensqualität von Kindern der Verumgruppe war nach OIT signifikant verbessert, jedoch nicht bei Kindern der Placebogruppe. Während der OIT wurde die Therapie von fast allen Kindern (82%) und Müttern (82%) als positiv bewertet (= niedrige Therapiebelastung).
Diskussion: Die EN-OIT führte bei einem Großteil der EN-allergischen Kinder zu einer Desensibilisierung und einer deutlich erhöhten Reaktionsschwelle auf EN. Somit sind die Kinder im Alltag vor akzidentellen Reaktionen auf EN geschützt, was die Lebensqualität der Kinder deutlich verbessert. Unter den kontrollierten Studienbedingungen zeigte sich ein akzeptables Sicherheitsprofil, mit vorrangig milder Symptomatik. Die klinische Desensibilisierung ging mit Veränderungen auf immunologischer Ebene einher. Langzeitstudien zur EN-OIT müssen jedoch abgewartet werden, um die klinische und immunologische Wirksamkeit hinsichtlich einer möglichen langfristigen oralen Toleranzinduktion sowie die Sicherheit unter langfristiger OIT zu untersuchen, bevor das Therapiekonzept in die Praxis übertragen werden kann.